Biochemical studies of the pathogenesis of emphysema in men in the British coal industry

In coalminers, exposure to respirable dust is associated with impairment of lung function.Possibly this impairment of function in part represents emphysema, since the frequency of emphysema in coalminers is higher than in other occupational groups. The most favoured hypothesis for the mechanism of causation of emphysema in the general population is that the elastase/anti-elastase balance in the lung is sufficiently disturbed to result in an excess of elastolytic activity leading to permanent damage to the elastin fibres of the lung. The cross-sectional study reported here set out to determine whether free elastase activity in sputum was related to lung function and radiographic evidence of emphysema in coalminers from three geographic areas of Britain. Preliminary studies of the influence of smoking and dust exposure on sputum elastase were also planned. During the course of the work, an opportunity arose to include men from neighbouring Post Office and Telecommunications (PO/Telecom) facilities, to provide comparisons with non-dust exposed populations. A total of 282 miners and 57 PO/Telecom men provided sputum samples.Sputum samples were sent by post direct to the laboratory in Edinburgh where sol phase elastase activity was measured in a radioassay using an ‘1 2 5 I-labelled elastin substrate and in a photometric assay using the synthetic substrate (free elastase assay) succinyl-alanyl-alanyl-alanine-p-nitroanilide (SLAPN) which measures both free elastase activity and that bound to alpha-2-macroglobulin (total elastase assay). Chest radiographs and lung function tests (forced expiratory flow/volume manoeuvres and single breath gas transfer measurements) were carried out on all participants. The results of lung function measurements were combined by a principal components analysis to provide three new quantities representing (1) a general measure of lung function, (2) degree of airflow obstruction or restriction, and (3) gas transfer ability.In a specially selected group of miners, blood serum was analysed for the level and phenotype of alpha-1-antiprotease (alPi), the major serum inhibitor of neutrophil-derived elastase. The principal findings were as follows:-1. Raised sputum elastase levels (both assays) were associated with impaired lung function, as measured by FEVj. The first component residual which gives a general measure of lung function, was related to elastase as measured by the artificial substrate (SLAPN) assay but not the radiolabelled elastin assay.2. Sputum elastase levels were not associated with lifetime cumulative exposure to respirable coalmine dust.3. In general, the greater part of the elastase activity in any sample was inhibitable by alPi, thus showing that most of the elastase was derived from neutrophils.4. In that part of the study in which alPi was measured in the serum of a subgroup of miners, we found that alPi level increased with age, and that, overall, alPi tended to decrease as dust exposure increased. In the 15% of this subgroup who gave sputum samples, free elastase (radiolabelled elastin assay), but not total elastase (SLAPN assay), increased as serum alPi increased.There was no association between rarer alPi (MS, MZ, SS) phenotypes and poor lung function.The ZZ phenotype was not found.5. Current smoking was found to be associated with low levels of total, but not of free, sputum elastase. However, the impact of smoking on elastase activity is difficult to gauge in this study because of the relatively low numbers of non-smokers (12%), and because they were untypical of non-smokers generally by virtue of their ability to produce sputum samples.6. The likely effects of postal travel on sputum elastase activity were examined in an additional study using sputum from hospitalised bronchitis patients. It was concluded that a journey time of two days would, in general, result in an increase in activity of both serine elastase (from neutrophils) and metallo-elastase (from bacteria and macrophages); and the nature and magnitude of the observed changes would be more likely to mask a real association in the main study than to create a false one.In conclusion, the finding of an association between sputum elastase and diminished lung function is consistent with the elastase/anti-elastase theory of emphysema pathogenesis, but does not prove a causal link for which a prospective study would be necessary There was no association between lifetime cumulative dust exposure and sputum elastase. In an additional study at one colliery we found a negative relationship between dust exposure and serum levels of alpha-1-antiprotease. On the basis of these findings we believe a prospective study of sputum elastase activity and lung function in coal miners would be extremely worthwhile. “”